Stimulatory effect of theophylline on regulation of fetal breathing movements.
We have performed the fetal CO2 response test on eight mature lambs in utero and have found that theophylline is a respiratory stimulant over a wide range of PaO2 and pHa. Theophylline produces significant increase in slope of P100, Pmax, and VEq response curves and significant increase in P100, Pmax, f, and VEq responses at PaCO2, 65 torr. It also produces significant lowering of the naturally high fetal absolute threshold to CO2, i.e., PaCO2 at which breathing starts during the CO2 test. "Offset" threshold, i.e., PaCO2 when breathing stops after the test, is the same with and without theophylline and equal to absolute threshold with theophylline. Our studies indicate that: (1) theophylline lowers fetal threshold and increases sensitivity to CO2; (2) increased sensitivity is expressed mainly by heightened Pmax (i.e., the equivalent of tidal volume) with some contribution of f particularly at high PaCO2; (3) decreased CO2 threshold is best assessed by determination of absolute threshold rather than the conventional x-axis intercept method; (4) the low offset threshold is consistent with our understanding that arousal is a requisite for generation and maintenance of fetal breathing; (5) theophylline is as effective a respiratory stimulant during fetal acidemia and hypoxemia as it is under normal conditions; and (6) a number of serious reservations must be held regarding use of theophylline during low pHa, low PaO2 states.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide; D005318:Fetal Heart / Q000187:drug effects; D005333:Fetus / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D009068:Movement / Q000187:drug effects; D012119:Respiration / Q000187:drug effects*; D012756:Sheep; D013806:Theophylline / Q000494:pharmacology*
D002245:Carbon Dioxide; D013806:Theophylline